还原叶酸载体基因G80A多态性与急性淋巴细胞白血病患儿甲氨蝶呤血药浓度及不良反应的关系研究  

Association Between RFC1 G80A Polymorphism and Plasma Concentration and Adverse Reactions of Methotrexate in Children with Acute Lymphoblastic Leukemia

作　　者：许静[1] 徐康康[1] 李天媛[1] 顾海娟[2] 廖清船[1] 杨力[3] 

机构地区：[1]南京医科大学附属南京儿童医院,南京市210008 [2]江苏南通市肿瘤医院药剂科,南通市226361 [3]南京医科大学第一附属医院普外科,南京市210029

出　　处：《中国药房》2009年第35期2739-2742,共4页China Pharmacy

基　　金：江苏省卫生厅医学科技发展基金会临床药学科研项目(200706);江苏省高校自然科学基础研究面上项目(08KJB320004)

摘　　要：目的:研究还原叶酸载体基因(RFC1)G80A多态性与急性淋巴细胞白血病患儿甲氨蝶呤(MTX)血药浓度及不良反应的关系。方法:筛选急性淋巴细胞白血病患儿101例。采用聚合酶链反应-限制性片断长度多态性方法(PCR-RFLP)分析患儿RFC1G80A基因型,运用荧光偏振免疫分析法(FPIA)测定MTX血药浓度,同时观察患儿的不良反应。结果:相对野生基因型携带者,携有突变基因型的患儿MTX血药浓度高,RFC1G80A基因型与MTX不良反应的发生率无明显相关。发生排泄延迟的患儿MTX不良反应发生率较高。结论:影响MTX不良反应个体间差异的因素复杂,对单纯由于RFC1G80A多态性导致的血药浓度增高患者,须谨慎调整甲酰四氢叶酸钙解救方案。OBJECTIVE： To investigate the association between reduced folate carrier 1 （RFC1） G80A polymorphism and plasma concentration and the adverse reaction of methotrexate （MTX） in children with acute lymphoblastic leukemia. METHODS： A total of 101 children with acute lymphoblastic leukemia were recruited. PCR- RFLP was used to determine the genotypes of RFC1 G80A polymorphism, and fluorescence polarization Immunoassay （FPIA） was employed to determine the plasma concentration of MTX. The toxicity response of the patients was observed. RESULTS： Compared with the wild- type genotype carriers, the mutant gene carriers had high plasma MTX concentration. The incidence rate of adverse reactions in- duced by MTX had no significant correlation with RFC1 G80A polymorphism. Children with elimination delay of MTX had high incidence rate of adverse reactions induced by MTX. CONCLUSION： The factors which could influence the interindi- vidual variation in adverse reactions of MTX were complicated. The calcium formyltetrahydrofolate salvage regimen should be carefully adjusted if high plasma concentration of MTX was caused simply by RFC1 G80A polymorphism.

关 键 词：还原叶酸载体 基因多态性 甲氨蝶呤 血药浓度 

分 类 号：R969.3[医药卫生—药理学]